Iressa Shows Promise For Treatment of Metastatic Breast Cancer When Combined With Hormonal Therapy

Gefitinib, the once-promising drug formerly approved as a second line treatment for lung cancer, also known as Iressa, enhanced the effectiveness of hormonal therapy for the treatment of specific types of metastatic breast cancer, according to a Phase II clinical trial led by researchers at The University of Texas M. D. Anderson Cancer Center.

These findings are surprising and represent the first positive study for Iressa in breast cancer, as well as for the entire class of drugs known as epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors, said Massimo Cristofanilli, M.D., the study's principal investigator.

Cristofanilli will present the findings at the American Society for Clinical Oncology's (ASCO) upcoming annual meeting as an oral presentation.

"We initiated this study in 2003 with hopes of reducing the resistance to hormonal therapy," said Cristofanilli. "There was a lot of preclinical work indicating that, in fact, resistance to hormonal therapy is strongly associated with an activated EGFR pathway. Also, EGFR over-expression has been associated with endocrine resistance. If there's a double blockage of the EGFR and the estrogen receptor, you may achieve better control of the disease."

The Phase II study enrolled 93 women from 30 centers across the United States and Latin America, with M. D. Anderson enrolling 20 patients. All of the women were newly diagnosed with metastatic breast cancer and were hormone receptor positive and estrogen receptor HER-2 negative. Patients were randomized to receive the aromatase inhibitor Arimidex (1 milligram) and Iressa (250 milligram) daily or Arimidex and placebo. The primary endpoint was progression-free survival.

When the study was unblinded, the researchers were surprised by the distinct findings: in the women who received Arimidex and Iressa, progression-free survival was 14.5 months, compared to 8.2 months in the women who did not receive Iressa, representing a 45 percent reduction in risk.

Additionally, of the women taking the combination, 47 percent had stable disease for more than 24 weeks and 49 percent had a clinical benefit. In contrast, 22 percent of the women had taking Arimidex alone had stable disease for more than 24 weeks and 34 percent had a clinical benefit.

Patients in the combination arm did have a higher rate of adverse events, but Cristofanilli notes that overall Iressa was very well tolerated.

"To see such a difference in such a small subset of patients was tremendously surprising," said Cristofanilli. "These findings show the possibility of adding a targeted therapy such as Iressa or others in the EGFR drug class to improve the benefit for hormonal therapy, giving another option for women who are hormone receptor positive, Her-2 negative with metastatic disease."

About 60 percent of women with breast cancer are hormone receptor positive and Her-2 negative, said Cristofanilli.